H-2I and HLA-D region cloned cDNA sequences will be utilized to isolate genomic DNA sequences. These genomic DNA clones will then be utilized to isolate adjacent genomic clones by the technique of "walking". Once adjacent genomic clones spanning a distance of 70-130 kb have been isolated, these denomic clones will be used to probe messenger RNA from appropriate cell sources to detect rare mRNAs encoding H-2I and HLA-D region gene sequences that are either known to exist (eg. Aa, Ab, AeE) or postulated to exist (I-J1,2,3, I-C) on the basis of serologic evidence, as well as to search for previously undetected I region gene products. Restriction fragments of these genomic DNA clones will be used to deduce open translational reading frames. The amino acid sequence deduced from DNA sequences of these open reading frames will be used to decide which amino acid sequences will be utilized in the production of synthetic amino acid oligomers which can then be coupled to immunogenic carriers to elicit specific antibody against such postulated or known gene products. These antibodies will then be used to characterize the structure and function of these gene products for both I region gene products and for the I region invariant polypeptide chain Ii of unknown linkage. Finally, a large library of monoclonal antibodies against specified subregions and alleles of the I region will be produced to facilitate the development of immunotherapy protocols for immunosuppression of the immune response and for immunoregulation of experimental autoimmune diseases in the mouse.